Neurotransmitter-Mediated Control of Neuronal Firing in the Red Nucleus of the Rat: Reciprocal Modulation between Noradrenaline and GABA

Abstract

The electrical activity of neurons from the red nucleus, a mesencephalic structure involved in motor control, is under the influence of several neurotransmitters released from afferent fibers and/or from local interneurons. We have investigated the combined effects of γ-aminobutyric acid (GABA) and noradrenaline (NA), both present at high levels in the red nucleus, on the firing activity of single rubral neurons recorded extracellularly in vivo on anesthetized adult rats. NA inhibited the firing activity of a large part of rubral neurons and induced excitatory or biphasic inhibitory/excitatory effects in a smaller group of cells. Neuronal firing was also inhibited by GABA in all the cells studied. When the effect of GABA was tested during continuous applications of NA, the magnitude of GABA response was modified in 58% of the cells: the effect of GABA was potentiated by NA in half of the responding neurons and was decreased in the remaining half. NA-induced potentiation of GABA response was mimicked by the α2-adrenoceptor agonist clonidine and was abolished by the α2-adrenoceptor antagonist yohimbine. On the other side, the decrease of GABA response was reproduced by the β-adrenoceptor agonist isoprenaline and was blocked by timolol, an antagonist of β-adrenoceptors. Neuronal firing activity was reduced by nipecotic acid, an inhibitor of GABA reuptake mechanism, and was instead increased during application of the GABAA receptor antagonist bicuculline, suggesting that rubral neurons in vivo were under tonic control by endogenous GABA. Both the inhibitory and the excitatory effects of NA were reduced in the presence of nipecotic acid and were instead potentiated during application of bicuculline, suggesting that NA responses were modified by endogenous GABA. Taken together, our results indicate a reciprocal modulation between the effects of GABA and NA on neuronal firing activity in the red nucleus of the rat: GABA depresses the responsiveness of rubral neurons to NA, whereas NA is able either to potentiate or to decrease the effects of GABA by activation of α2- and β-adrenoceptors, respectively. The functional significance of such interaction, as well as the possible implication in diseases affecting motor control, will be discussed.